Interferon action in triply deficient mice reveals the existence of alternative antiviral pathways - PubMed (original) (raw)
. 1999 Jun 5;258(2):435-40.
doi: 10.1006/viro.1999.9738.
Affiliations
- PMID: 10366581
- DOI: 10.1006/viro.1999.9738
Free article
Interferon action in triply deficient mice reveals the existence of alternative antiviral pathways
A Zhou et al. Virology. 1999.
Free article
Abstract
Antiviral proteins encoded by the interferon (IFN)-stimulated genes provide a front-line defense against viral infections. In particular, PKR, RNase L, and Mx are considered to be the principal proteins through which IFNs mount an antiviral state. To determine whether alternative antiviral pathways exist, RNase L-/- mice and PKR-/- mice were crossed onto an Mx1(-/-) background to generate a strain of triply deficient (TD) mice. After infections with encephalomyocarditis virus, the TD mice died 3-4 days earlier than infected, wild-type mice. However, there was an IFN dose-dependent increase in survival times after encephalomyocarditis virus infections for both the TD and wild-type mice. Mice that were deficient for PKR or RNase L showed intermediate survival times between those of the TD and wild-type mice. Surprisingly, cultured embryonic fibroblasts lacking RNase L, PKR, or both proteins were still able to mount a substantial residual antiviral response against encephalomyocarditis virus or vesicular stomatitis virus after IFN-alpha treatments. These results confirm the antiviral functions of RNase L and PKR in vivo but also provide unequivocal evidence for the existence of novel, innate immune pathways against viruses.
Copyright 1999 Academic Press.
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